Serotonin Receptor Binding and Sudden Infant Death Syndrome

5/30/2023

Letter from Tom Keens, MD, to the California SIDS community.

An important research study was recently published by Robin Haynes and her colleagues at Harvard. Doctor Haynes has continued the work of Professor Hannah Kinney on brainstem neurotransmitters and neurotransmitter receptor binding sites in the brainstems of babies dying from SIDS. The reference for the paper is:

Haynes, R.<., F. Trachtenberg, R. Darnall, E.A. Haas, R.D. Goldstein, O.J. Mena, J.F. Krous, and H.C. Kinney. Altered %-HT2A/C receptor binding in the sudden infant death syndrome: Part I. Tissue=based evidence for serotonin receptor signaling abnormalities in cardiorespiratory- and arousal-related circuits. Journal of Neuropathology and Experimental Neurology, doi.org/10.1093/jnen/nlad030, 2023.

A copy of the original research paper is appended here.

The Harvard group has previously described abnormalities in the brainstems of babies dying from sudden infant death syndrome (SIDS). Their more recent work focuses on serotonin. In addition, they previously reported decreased serotonin receptor binding sites in SIDS brainstems. Neurotransmitters, like serotonin, need to bind to a receptor in order to perpetuate a neural impulse. In this study, they found decreased serotonin receptor binding sites in many areas of SIDS brainstems, but especially those which control breathing, cardiac responses to environmental challenges, and arousal from sleep. Many investigators have postulated that SIDS babies might die because they fail to arouse or wake up in response to potentially dangerous situations while asleep. This study provides neuropathologic evidence that arousal and cardiorespiratory responses are decreased or even abnormal in SIDS babies.

Further, we know that SIDS is most common at age 2-4 months, and that there are fewer deaths in the first month of life. This is different from other natural causes of infant death, which are most common near birth and decrease as the infant ages. This study found that the number of serotonin receptor binding sites was closer to normal in SIDS brainstems at birth. However, in control brainstems (not SIDS) serotonin receptor binding sites increased with age in the first 10-months of life, but not in the SIDS brainstems. This may be a partial explanation for why SIDS is less common in the first month of life.

The investigators still hold to the Triple Risk hypothesis of SIDS, which suggests that SIDS is not a single abnormality in a single physiologic system. Rather, it is an interaction between age, intrinsic difference in vulnerability, and environmental challenges. Not all babies with decreased serotonin receptor binding sites will die, especially if they are not challenged with an environmental hazard during the critical developmental window. Nevertheless, this is an important study which further supports an inability or decreased ability of SIDS babies to respond to environmental hazards during sleep.

Jacklin Kwan, a reporter for a British publication NewScientist, interviewed both Robin Haynes and me for a lay article on this research (copy here).

Thank you so much for all you do to improve SIDS services, education, and research in California.

--- Tom Keens, Chair of the California SUDS Advisory Council

tkeensatchla.usc.edu